2023
Pembrolizumab versus methotrexate, docetaxel, or cetuximab in recurrent or metastatic head and neck squamous cell carcinoma (KEYNOTE-040): Subgroup analysis by pattern of disease recurrence
Harrington K, Cohen E, Soulières D, Dinis J, Licitra L, Ahn M, Soria A, Machiels J, Mach N, Mehra R, Burtness B, Swaby R, Lin J, Ge J, Lerman N, Tourneau C. Pembrolizumab versus methotrexate, docetaxel, or cetuximab in recurrent or metastatic head and neck squamous cell carcinoma (KEYNOTE-040): Subgroup analysis by pattern of disease recurrence. Oral Oncology 2023, 147: 106587. PMID: 37925894, DOI: 10.1016/j.oraloncology.2023.106587.Peer-Reviewed Original ResearchConceptsSubgroup analysisRecurrence patternsNeck squamous cell carcinomaDisease recurrence patternsPlatinum-containing treatmentSquamous cell carcinomaLonger OSProlonged OSAdvanced diseaseData cutoffDefinitive therapyMetastatic headDurable responsesHazard ratioDisease recurrenceMetastatic HNSCCTreatment armsCell carcinomaM diseaseInvestigator's choicePatientsPembrolizumabRecurrentOnly subgroupSubgroupsRandomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer
Bauman J, Saba N, Roe D, Bauman J, Kaczmar J, Bhatia A, Muzaffar J, Julian R, Wang S, Bearelly S, Baker A, Steuer C, Giri A, Burtness B, Centuori S, Caulin C, Klein R, Saboda K, Obara S, Chung C. Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer. Journal Of Clinical Oncology 2023, 41: 3851-3862. PMID: 36977289, DOI: 10.1200/jco.22.01994.Peer-Reviewed Original ResearchConceptsMedian progression-free survivalProgression-free survivalObjective response rateRecurrent/metastatic headCMET overexpressionMetastatic headCombination armAntiepidermal growth factor receptor monoclonal antibodyNoncomparative phase II studyRecurrent/metastatic HNSCCRandomized phase II trialEnd pointNeck squamous cell carcinomaHPV negative subgroupPhase II studyPrimary end pointSecondary end pointsHPV-positive diseaseHuman papillomavirus (HPV) statusMajor prognostic factorPhase II trialKey eligibility criteriaSquamous cell carcinomaReceptor monoclonal antibodyHPV-negative HNSCC
2022
Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study
Harrington KJ, Burtness B, Greil R, Soulières D, Tahara M, de Castro G, Psyrri A, Brana I, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesia R, Ngamphaiboon N, Rordorf T, Ishak W, Lin J, Gumuscu B, Swaby RF, Rischin D. Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Journal Of Clinical Oncology 2022, 41: 790-802. PMID: 36219809, PMCID: PMC9902012, DOI: 10.1200/jco.21.02508.Peer-Reviewed Original ResearchConceptsPD-L1 CPSNeck squamous cell carcinomaSquamous cell carcinomaRecurrent/metastatic headMetastatic headCell carcinomaOverall survivalNext-line therapyObjective response ratePembrolizumab-based therapyProgression-free survivalDeath ligand 1Long-term efficacyKEYNOTE-048Data cutoffSurvival benefitTotal populationMedian studyPembrolizumabResponse rateCarcinomaPositive scoreLigand 1Subsequent treatmentEfficacy
2020
Reply to “Keynote 48: Is it really for everyone?”
Burtness B, Ge J. Reply to “Keynote 48: Is it really for everyone?”. Oral Oncology 2020, 112: 104983. PMID: 33032941, DOI: 10.1016/j.oraloncology.2020.104983.Peer-Reviewed Original ResearchQuality of Life With Pembrolizumab for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: KEYNOTE-040
Harrington KJ, Soulières D, Le Tourneau C, Dinis J, Licitra LF, Ahn MJ, Soria A, Machiels JH, Mach N, Mehra R, Burtness B, Ellison MC, Cheng JD, Chirovsky DR, Swaby RF, Cohen EEW. Quality of Life With Pembrolizumab for Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: KEYNOTE-040. Journal Of The National Cancer Institute 2020, 113: 171-181. PMID: 32407532, PMCID: PMC7850527, DOI: 10.1093/jnci/djaa063.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCetuximabDisease-Free SurvivalDocetaxelHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalPatient Reported Outcome MeasuresQuality of LifeSquamous Cell Carcinoma of Head and NeckConceptsGHS/QoL scoresStandard of careNeck squamous cell carcinomaGlobal health statusSquamous cell carcinomaQOL scoresWeek 15KEYNOTE-040Metastatic HNSCCCell carcinomaNeck cancer-specific modulePlatinum-containing regimenHealth-related qualityCancer-specific moduleQuality of lifeHRQoL benefitsHRQoL populationMetastatic headHRQoL analysisMedian timeLife HeadPembrolizumabPatientsHealth statusEuropean Organization
2019
Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma
Baro M, Lopez Sambrooks C, Burtness BA, Lemmon MA, Contessa JN. Neuregulin Signaling Is a Mechanism of Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma. Molecular Cancer Therapeutics 2019, 18: 2124-2134. PMID: 31387891, PMCID: PMC6825559, DOI: 10.1158/1535-7163.mct-19-0163.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalCell Line, TumorCell ProliferationCell SurvivalCetuximabDrug Resistance, NeoplasmFemaleHead and Neck NeoplasmsHumansMiceNeuregulinsProto-Oncogene Proteins c-aktReceptor, ErbB-3Signal TransductionSquamous Cell Carcinoma of Head and NeckUp-RegulationXenograft Model Antitumor AssaysConceptsNeck squamous cell carcinomaSquamous cell carcinomaTherapeutic resistanceCell carcinomaResistant cellsConcentrations of cetuximabEFM-19 cellsCetuximab-resistant cellsActionable therapeutic targetsHNSCC cell linesTumor growth experimentsInhibition of EGFRErbB3 antibodyNeuregulin expressionOverall survivalTreatment regimensCetuximab resistanceTherapeutic targetAutocrine loopLocal controlTumor growthRadiotherapyEGFR inhibitionCetuximabNeuregulin SignalingPembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, Psyrri A, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesía R, Ngamphaiboon N, Rordorf T, Ishak W, Hong RL, Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D, Investigators K, Lerzo G, Tatangelo M, Varela M, Zarba J, Boyer M, Gan H, Gao B, Hughes B, Mallesara G, Rischin D, Taylor A, Burian M, Fuereder T, Greil R, Barrios C, de Castro D, Castro G, Franke F, Girotto G, Lima I, Nicolau U, Pinto G, Santos L, Victorino A, Chua N, Couture F, Gregg R, Hansen A, Hilton J, McCarthy J, Soulieres D, Ascui R, Gonzalez P, Villanueva L, Torregroza M, Zambrano A, Holeckova P, Kral Z, Melichar B, Prausova J, Vosmik M, Andersen M, Gyldenkerne N, Jurgens H, Putnik K, Reinikainen P, Gruenwald V, Laban S, Aravantinos G, Boukovinas I, Georgoulias V, Psyrri A, Kwong D, Al-Farhat Y, Csoszi T, Erfan J, Horvai G, Landherr L, Remenar E, Ruzsa A, Szota J, Billan S, Gluck I, Gutfeld O, Popovtzer A, Benasso M, Bui S, Ferrari V, Licitra L, Nole F, Fujii T, Fujimoto Y, Hanai N, Hara H, Matsumoto K, Mitsugi K, Monden N, Nakayama M, Okami K, Oridate N, Shiga K, Shimizu Y, Sugasawa M, Tahara M, Takahashi M, Takahashi S, Tanaka K, Ueda T, Yamaguchi H, Yamazaki T, Yasumatsu R, Yokota T, Yoshizaki T, Kudaba I, Stara Z, Ishak W, Cheah S, Ponce J, Mendoza R, Hernandez C, Soto F, Buter J, Hoeben A, Oosting S, Suijkerbuijk K, Bratland A, Brydoey M, Alvarez R, Mas L, Caguioa P, Querol J, Regala E, Tamayo M, Villegas E, Kawecki A, Karpenko A, Klochikhin A, Smolin A, Zarubenkov O, Goh B, Cohen G, du Toit J, Jordaan C, Landers G, Ruff P, Szpak W, Tabane N, Brana I, Docampo L, Lavernia J, Mesia R, Abel E, Muratidu V, Nielsen N, Cristina V, Rordorf T, Rothschild S, Hong R, Wang H, Yang M, Yeh S, Yen C, Ngamphaiboon N, Soparattanapaisarn N, Sriuranpong V, Aksoy S, Cicin I, Ekenel M, Harputluoglu H, Ozyilkan O, Harrington K, Agarwala S, Ali H, Alter R, Anderson D, Bruce J, Burtness B, Campbell N, Conde M, Deeken J, Edenfield W, Feldman L, Gaughan E, Goueli B, Halmos B, Hegde U, Hunis B, Jotte R, Karnad A, Khan S, Laudi N, Laux D, Martincic D, McCune S, McGaughey D, Misiukiewicz K, Mulford D, Nadler E, Neupane P, Nunnink J, Ohr J, O'Malley M, Patson B, Paul D, Popa E, Powell S, Redman R, Rella V, Lima C, Sivapiragasam A, Su Y, Sukari A, Wong S, Yilmaz E, Yorio J. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. The Lancet 2019, 394: 1915-1928. PMID: 31679945, DOI: 10.1016/s0140-6736(19)32591-7.Peer-Reviewed Original ResearchConceptsCombined positive scoreSecond interim analysisProgression-free survivalPD-L1 combined positive scoreAppropriate first-line treatmentFirst-line treatmentOverall survivalSquamous cell carcinomaChemotherapy groupMetastatic HNSCCInterim analysisAdverse eventsAlone groupCell carcinomaFinal analysisCell death ligand 1 (PD-L1) expressionDeath ligand 1 (PD-L1) expressionMetastatic squamous cell carcinomaNeck squamous cell carcinomaCause adverse eventsPD-L1 positivityLigand 1 expressionPD-L1 expressionTotal populationIncurable recurrentPTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma
Eze N, Lee JW, Yang DH, Zhu F, Neumeister V, Sandoval-Schaefer T, Mehra R, Ridge JA, Forastiere A, Chung CH, Burtness B. PTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma. Oral Oncology 2019, 91: 69-78. PMID: 30926065, PMCID: PMC6855599, DOI: 10.1016/j.oraloncology.2019.02.026.Peer-Reviewed Original ResearchConceptsNeck squamous cell carcinomaEpidermal growth factor receptorSquamous cell carcinomaCell carcinomaCetuximab-based therapyTrial of cisplatinTrials (RCTs) of cetuximabPotential predictive biomarkersPTEN expressionLack of benefitPI3K mutationsPI3K p110αHigh PTEN expressionPI3K pathwayGrowth factor receptorHot spot mutationsStandard therapySuperior PFSMultivariable analysisPredictive biomarkersLoss of expressionSuch therapyCommon abnormalityCetuximabSide effects
2018
Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study
Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ, investigators K, Acosta-Rivera M, Adkins D, Aghmesheh M, Ahn M, Airoldi M, Aleknavicius E, Al-Farhat Y, Algazi A, Almokadem S, Alyasova A, Bauman J, Benasso M, Berrocal A, Bray V, Burtness B, Caponigro F, Castro A, Cescon T, Chan K, Chaudhry A, Chauffert B, Cohen E, Csoszi T, De Boer J, Delord J, Dietz A, Dinis J, Dupuis C, Digue L, Erfan J, Alvarez Y, Evans M, Fidler M, Forster M, Friesland S, Ganti A, Geoffrois L, Grant C, Gruenwald V, Harrington K, Hoffmann T, Horvai G, Inciura A, Jang R, Jankowska P, Jimeno A, Joseph M, Ramiro A, Karaszewska B, Kawecki A, Keilholz U, Keller U, Kim S, Kocsis J, Kotecki N, Kozloff M, Lambea J, Landherr L, Lantsukhay Y, Lazarev S, Lee L, Le Tourneau C, Licitra L, Lifirenko I, Mach N, Martincic D, Matorin O, McGrath M, Machiels J, Mehra R, Misiukiewicz K, Morris J, Mufazalov F, Niu J, Srinivasan D, Segura P, Rauch D, Ribeiro M, Rodriguez C, Rolland F, Russo A, Ruzsa A, Sanches F, Shin S, Shtiveland M, Soulieres D, Soria A, Specenier P, Szekanecz E, Szota J, van Herpen C, Velez-Cortes H, Walsh W, Wilop S, Winterhalder R, Wojtukiewicz M, Wong D, Zandberg D. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. The Lancet 2018, 393: 156-167. PMID: 30509740, DOI: 10.1016/s0140-6736(18)31999-8.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCetuximabDisease ProgressionDocetaxelDrug Administration ScheduleFemaleHead and Neck NeoplasmsHumansKaplan-Meier EstimateMaleMethotrexateMiddle AgedNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckConceptsNeck squamous cell carcinomaSquamous cell carcinomaStandard of careTreatment-related adverse eventsCell carcinomaMetastatic headOverall survivalTreat populationAdverse eventsCommon treatment-related adverse eventsWorse treatment-related adverse eventsPlatinum-containing treatmentTreatment-related deathsMedian overall survivalWeb response systemEffective treatment optionFavorable safety profileEarly phase trialsTreatment of headSubsidiary of MerckManageable toxicityMeaningful prolongationAdvanced diseasePrimary endpointMetastatic diseaseRadiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial
Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, Jones CU, Dunlap NE, Seaward SA, Spencer S, Galloway TJ, Phan J, Dignam JJ, Le QT. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. The Lancet 2018, 393: 40-50. PMID: 30449625, PMCID: PMC6541928, DOI: 10.1016/s0140-6736(18)32779-x.Peer-Reviewed Original ResearchConceptsHPV-positive oropharyngeal carcinomaProgression-free survivalOverall survivalNon-inferiority trialCisplatin groupCetuximab groupOropharyngeal carcinomaSevere toxicityEligibility criteriaPositive oropharyngeal squamous cell carcinomaHuman papillomavirus-positive oropharyngeal cancerNational Cancer Institute-USAZubrod performance status 0Oropharyngeal squamous cell carcinomaAdequate bone marrowPerformance status 0Replacement of cisplatinZubrod performance statusInferior overall survivalTobacco smoking historyAmerican Joint CommitteeNon-inferiority criteriaSquamous cell carcinomaStandard of careNon-inferiority margin
2016
E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx— ECOG-ACRIN Cancer Research Group
Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, Westra WH, Gilbert J, Bauman JE, Wagner LI, Trevarthen DR, Balkrishna J, Murphy BA, Agrawal N, Colevas AD, Chung CH, Burtness B. E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx— ECOG-ACRIN Cancer Research Group. Journal Of Clinical Oncology 2016, 35: 490-497. PMID: 28029303, PMCID: PMC5455313, DOI: 10.1200/jco.2016.68.3300.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCetuximabChemoradiotherapyDisease-Free SurvivalDrug Administration ScheduleExanthemaFemaleHuman papillomavirus 16HumansInduction ChemotherapyMaleMiddle AgedNeutropeniaOropharyngeal NeoplasmsPapillomavirus InfectionsRadiotherapy DosageRemission InductionConceptsOropharyngeal squamous cell carcinomaComplete clinical responseCycle of ICPhase II trialProgression-free survivalSquamous cell carcinomaWeekly cetuximabII trialCell carcinomaPack-year smoking historyResectable squamous cell carcinomaFavorable-risk patientsPrimary end pointOverall survival rateHigh cure ratesCancer Research GroupGy of radiationRadiation doseLong-term toxicityRadiation dose reductionChemoradiation resultsICS respondersInduction chemotherapyLate sequelaeClinical responseCALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers
Enzinger PC, Burtness BA, Niedzwiecki D, Ye X, Douglas K, Ilson DH, Villaflor VM, Cohen SJ, Mayer RJ, Venook A, Benson AB, Goldberg RM. CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and Gastroesophageal Junction Cancers. Journal Of Clinical Oncology 2016, 34: 2736-2742. PMID: 27382098, PMCID: PMC5019745, DOI: 10.1200/jco.2015.65.5092.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCamptothecinCarcinoma, Squamous CellCetuximabCisplatinDisease ProgressionDisease-Free SurvivalEpirubicinEsophageal NeoplasmsEsophagogastric JunctionFemaleFluorouracilHumansIrinotecanLeucovorinMaleMiddle AgedOrganoplatinum CompoundsSurvival RateTime FactorsTreatment FailureConceptsGastroesophageal junction cancerProgression-free survivalMetastatic esophagealJunction cancerOverall survivalTreatment failureResponse rateMedian progression-free survivalRandomized phase II studyContinuous infusion fluorouracilOptimal chemotherapy backboneTreatment-related deathsMedian overall survivalPhase II studyPrimary end pointCooperative group studiesPromising preclinical dataChemotherapy backboneChemotherapy regimensAdverse eventsII studySecondary outcomesMedian timeTreatment armsPreclinical dataRandomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus Cetuximab for Metastatic Pancreatic Cancer
Burtness B, Powell M, Catalano P, Berlin J, Liles DK, Chapman AE, Mitchell E, Benson AB. Randomized Phase II Trial of Irinotecan/Docetaxel or Irinotecan/Docetaxel Plus Cetuximab for Metastatic Pancreatic Cancer. American Journal Of Clinical Oncology 2016, 39: 340-345. PMID: 24685886, PMCID: PMC4177955, DOI: 10.1097/coc.0000000000000068.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAgedAnticoagulantsAntineoplastic Combined Chemotherapy ProtocolsCA-19-9 AntigenCamptothecinCetuximabDiarrheaDisease-Free SurvivalDocetaxelEnoxaparinFemaleHumansIrinotecanMaleMiddle AgedPancreatic NeoplasmsResponse Evaluation Criteria in Solid TumorsSurvival RateTaxoidsThromboembolismConceptsProgression-free survivalMetastatic pancreatic cancerAddition of cetuximabGrade 3/4 toxicitiesOverall survivalArm APancreatic cancerResponse rateArm B.Arm B. Median progression-free survivalMedian progression-free survivalPrincipal grade 3/4 toxicitiesRandomized phase II trialIrinotecan/docetaxelPhase II trialEligible patientsII trialPrimary endpointSecondary endpointsThromboembolic eventsDocetaxel combinationIrinotecan combinationObjective responseIrinotecan therapyMetastatic adenocarcinoma
2014
Phase II Study of Cetuximab in Combination with Cisplatin and Radiation in Unresectable, Locally Advanced Head and Neck Squamous Cell Carcinoma: Eastern Cooperative Oncology Group Trial E3303
Egloff AM, Lee JW, Langer CJ, Quon H, Vaezi A, Grandis JR, Seethala RR, Wang L, Shin DM, Argiris A, Yang D, Mehra R, Ridge JA, Patel UA, Burtness BA, Forastiere AA. Phase II Study of Cetuximab in Combination with Cisplatin and Radiation in Unresectable, Locally Advanced Head and Neck Squamous Cell Carcinoma: Eastern Cooperative Oncology Group Trial E3303. Clinical Cancer Research 2014, 20: 5041-5051. PMID: 25107914, PMCID: PMC4184913, DOI: 10.1158/1078-0432.ccr-14-0051.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCetuximabCisplatinDisease ProgressionFemaleHead and Neck NeoplasmsHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm StagingRadiotherapyRisk FactorsSquamous Cell Carcinoma of Head and NeckTreatment OutcomeConceptsProgression-free survivalOverall survivalLA-SCCHNMaintenance cetuximabAdvanced squamous cell headMedian progression-free survivalTwo-year overall survivalNeck squamous cell carcinomaTumor human papillomavirus (HPV) statusGrade 5 toxicityMedian overall survivalMedian radiotherapy doseMost common gradeCycles of cisplatinHuman papillomavirus (HPV) statusPhase II studySquamous cell headTumor HPV statusLonger overall survivalSquamous cell carcinomaOropharyngeal primaryHPV statusII studyPrimary endpointProtocol treatmentA 3′-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma
Chung CH, Lee JW, Slebos RJ, Howard JD, Perez J, Kang H, Fertig EJ, Considine M, Gilbert J, Murphy BA, Nallur S, Paranjape T, Jordan RC, Garcia J, Burtness B, Forastiere AA, Weidhaas JB. A 3′-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Annals Of Oncology 2014, 25: 2230-2236. PMID: 25081901, PMCID: PMC4207729, DOI: 10.1093/annonc/mdu367.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedCarcinoma, Squamous CellCetuximabCisplatinCyclin-Dependent Kinase Inhibitor p16Disease-Free SurvivalDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGenotypeHead and Neck NeoplasmsHumansMaleMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalPrognosisProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)Ras ProteinsSquamous Cell Carcinoma of Head and NeckConceptsNeck squamous cell carcinomaSquamous cell carcinomaKRAS-variantMetastatic headCell carcinomaPatient outcomesP16 expressionRecurrent/metastatic headPoor progression-free survivalCell linesM HNSCC patientsPlatinum-based regimenProgression-free survivalPotential predictive biomarkersHNSCC tumor samplesHNSCC cell linesTG/GGDrug resistance/sensitivityHNSCC patientsOropharynx tumorsClinical findingsRetrospective studyPredictive biomarkersClinical trialsPlatinum responseInduction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303)
Wanebo HJ, Lee J, Burtness BA, Ridge JA, Ghebremichael M, Spencer SA, Psyrri D, Pectasides E, Rimm D, Rosen FR, Hancock MR, Tolba KA, Forastiere AA. Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303). Annals Of Oncology 2014, 25: 2036-2041. PMID: 25009013, PMCID: PMC4176450, DOI: 10.1093/annonc/mdu248.Peer-Reviewed Original ResearchConceptsEvent-free survivalStage III/IV headResponse/survivalInduction therapyComplete responseStage III/IV HNSCCNeck squamous cell carcinomaPrimary site biopsiesTreatment-related deathsPathologic complete responseNeck squamous cancerSquamous cell carcinomaProtein expression statusEligible patientsSite biopsiesOverall survivalCell carcinomaPromising survivalSquamous cancerDisease progressionChemoradiationRadiation therapyPatientsWeek 9CetuximabPrognostic Biomarkers in Phase II Trial of Cetuximab-Containing Induction and Chemoradiation in Resectable HNSCC: Eastern Cooperative Oncology Group E2303
Psyrri A, Lee JW, Pectasides E, Vassilakopoulou M, Kosmidis EK, Burtness BA, Rimm DL, Wanebo HJ, Forastiere AA. Prognostic Biomarkers in Phase II Trial of Cetuximab-Containing Induction and Chemoradiation in Resectable HNSCC: Eastern Cooperative Oncology Group E2303. Clinical Cancer Research 2014, 20: 3023-3032. PMID: 24700741, PMCID: PMC4049169, DOI: 10.1158/1078-0432.ccr-14-0113.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarboplatinCarcinoma, Squamous CellCetuximabChemoradiotherapyDisease-Free SurvivalDrug Resistance, NeoplasmFemaleFluorescent Antibody TechniqueHead and Neck NeoplasmsHumansInduction ChemotherapyKaplan-Meier EstimateMaleMiddle AgedMitogen-Activated Protein Kinase KinasesPaclitaxelPhosphatidylinositol 3-KinasesPrognosisProportional Hazards ModelsProto-Oncogene Proteins c-aktRas ProteinsSignal TransductionSquamous Cell Carcinoma of Head and NeckTissue Array AnalysisConceptsProgression-free survivalEvent-free survivalPhase II trialOverall survivalII trialTissue microarrayStage III/IV headMultivariable Cox proportional hazards modelsMultivariable Cox regression analysisNeck squamous cell cancerRAS/MAPK/ERKCox proportional hazards modelInsulin-like growth factor 1 receptorLarge prospective studiesCox regression analysisInferior overall survivalKaplan-Meier methodSquamous cell cancerLog-rank testGrowth factor 1 receptorProportional hazards modelPI3K/Akt pathwayFactor 1 receptorPI3K/AktEGF receptor
2013
Novel targets in HPV-negative head and neck cancer: overcoming resistance to EGFR inhibition
Burtness B, Bauman JE, Galloway T. Novel targets in HPV-negative head and neck cancer: overcoming resistance to EGFR inhibition. The Lancet Oncology 2013, 14: e302-e309. PMID: 23816296, DOI: 10.1016/s1470-2045(13)70085-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCetuximabDrug DesignDrug Resistance, NeoplasmErbB ReceptorsHead and Neck NeoplasmsHistone Deacetylase InhibitorsHumansMolecular Targeted TherapyPapillomaviridaeProtein Kinase InhibitorsProto-Oncogene Proteins c-metReceptor, ErbB-2Signal TransductionTreatment OutcomeConceptsHPV-negative headNeck cancerHuman papillomavirusEGFR inhibitionSingle-agent cetuximabLow cure rateMonoclonal antibody cetuximabActive therapyCytotoxic chemotherapyDisease survivalCure rateMechanisms of resistanceAntibody cetuximabResponse rateCetuximabEGFRNovel targetReceptor tyrosine kinasesCancerTherapyHistone deacetylaseChemotherapyHabitual exposureModest effectNuclear functionsTargeting C4-Demethylating Genes in the Cholesterol Pathway Sensitizes Cancer Cells to EGF Receptor Inhibitors via Increased EGF Receptor Degradation
Sukhanova A, Gorin A, Serebriiskii IG, Gabitova L, Zheng H, Restifo D, Egleston BL, Cunningham D, Bagnyukova T, Liu H, Nikonova A, Adams GP, Zhou Y, Yang DH, Mehra R, Burtness B, Cai KQ, Klein-Szanto A, Kratz LE, Kelley RI, Weiner LM, Herman GE, Golemis EA, Astsaturov I. Targeting C4-Demethylating Genes in the Cholesterol Pathway Sensitizes Cancer Cells to EGF Receptor Inhibitors via Increased EGF Receptor Degradation. Cancer Discovery 2013, 3: 96-111. PMID: 23125191, PMCID: PMC3546138, DOI: 10.1158/2159-8290.cd-12-0031.Peer-Reviewed Original ResearchConceptsEGF receptorPathway genesDegradation of EGFROncogenic EGF receptorEGF receptor degradationBiosynthesis pathway genesPlatelet-derived growth factor receptorEndocytic traffickingVesicular traffickingEGF receptor inhibitorEGFR degradationDimerization partnerBioinformatics modelingGrowth factor receptorUnexpected roleReceptor degradationCancer cell viabilityNSDHLSC4MOLCholesterol pathwayGenesFactor receptorCancer resistanceEGFR antagonistsCancer cells
2012
Comment on “Epidermal Growth Factor Receptor Is Essential for Toll-Like Receptor 3 Signaling”
Burtness B, Marur S, Bauman JE, Golemis EA, Mehra R, Cohen SJ. Comment on “Epidermal Growth Factor Receptor Is Essential for Toll-Like Receptor 3 Signaling”. Science Signaling 2012, 5: lc5. PMID: 23233526, DOI: 10.1126/scisignal.2003734.Peer-Reviewed Original ResearchConceptsEpidermal growth factor receptorGrowth factor receptorToll-like receptor 3Functional innate immune responseFactor receptorInnate immune responseFulminant infectionCombination therapyImmune responseTumor growthReceptor 3Mammalian targetCancer therapeuticsReceptorsMTORPatientsBody of literatureTherapyTumorsInfection